Regulation of alternative splicing is one of the most efficient mechanisms to enlarge the proteomic diversity in eukaryotic organisms. Many viruses hijack the splicing machinery following infection to accomplish their replication cycle. Regarding the HBV, numerous reports have described alternative splicing events of the long viral transcript (pregenomic RNA), which also acts as a template for viral genome replication. Alternative splicing of HBV pregenomic RNAs allows the synthesis of at least 20 spliced variants. In addition, almost all these spliced forms give rise to defective particles, detected in the blood of infected patients. HBV-spliced RNAs have long been unconsidered, probably due to their uneasy detection in comparison to unspliced forms as well as for their dispensable role during viral replication. However, recent data highlighted the relevance of these HBV-spliced variants through (1) the trans-regulation of the alternative splicing of viral transcripts along the course of liver disease; (2) the ability to generate defective particle formation, putative biomarker of the liver disease progression; (3) modulation of viral replication; and (4) their intrinsic propensity to encode for novel viral proteins involved in liver pathogenesis and immune response. Altogether, tricky regulation of HBV alternative splicing may contribute to modulate multiple viral and cellular processes all along the course of HBV-related liver disease.

中文翻译：

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病毒转录本的可变剪接：HBV 的阴暗面

选择性剪接的调控是扩大真核生物蛋白质组多样性的最有效机制之一。许多病毒在感染后劫持剪接机制以完成其复制周期。关于 HBV，许多报道描述了长病毒转录物（前基因组 RNA）的可变剪接事件，它也可作为病毒基因组复制的模板。HBV 前基因组 RNA 的可变剪接允许合成至少 20 个剪接变体。此外，几乎所有这些拼接形式都会产生缺陷颗粒，在感染患者的血液中检测到。长期以来，HBV 剪接的 RNA 一直未被考虑，这可能是因为与未剪接的形式相比，它们不易检测，以及它们在病毒复制过程中的可有可无的作用。然而，最近的数据强调了这些 HBV 剪接变体的相关性，通过 (1) 肝病过程中病毒转录物选择性剪接的反式调节；(2) 产生缺陷颗粒形成的能力，肝脏疾病进展的推定生物标志物；(3) 病毒复制的调节；(4) 它们编码与肝脏发病机制和免疫反应有关的新型病毒蛋白的内在倾向。总而言之，HBV 选择性剪接的复杂调节可能有助于调节 HBV 相关肝病整个过程中的多种病毒和细胞过程。肝脏疾病进展的推定生物标志物；(3) 病毒复制的调节；(4) 它们编码与肝脏发病机制和免疫反应有关的新型病毒蛋白的内在倾向。总而言之，HBV 选择性剪接的复杂调节可能有助于调节 HBV 相关肝病整个过程中的多种病毒和细胞过程。肝脏疾病进展的推定生物标志物；(3) 病毒复制的调节；(4) 它们编码与肝脏发病机制和免疫反应有关的新型病毒蛋白的内在倾向。总而言之，HBV 选择性剪接的复杂调节可能有助于调节 HBV 相关肝病整个过程中的多种病毒和细胞过程。